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Anthropogenically-driven climate warming and land use change are the main causes of an ongoing decrease in global biodiversity. It is unclear how ecosystems, particularly freshwater habitats, will respond to such continuous and potentially intensifying disruptions. Here we analyse how different components of terrestrial and aquatic ecosystems responded to natural climate change during the Lateglacial. By applying a range of analytical techniques (sedimentology, palaeoecology, geochemistry) to the well-dated sediment archive from Lake Hämelsee (Germany), we show evidence for vegetation development, landscape dynamics and aquatic ecosystem change typical for northwest Europe during the Lateglacial. By particularly focussing on periods of abrupt climate change, we determine the timing and duration of changes in biodiversity in response to external forcing. We show that onsets of changes in biodiversity indicators (e.g. diatom composition, Pediastrum concentrations) lag changes in environmental records (e.g. loss-on-ignition) by a few decades, particularly at the Allerød/Younger Dryas transition. Most biodiversity indicators showed transition times of 10–50 years, whereas environmental records typically showed a 50–100 year long transition. In some cases, transition times observed for the compositional turnover or productivity records were up to 185 years, which could have been the result of the combined effects of direct (e.g. climate) and indirect (e.g. lake stratification) drivers of ecosystem change. Our results show differences in timing and duration of biodiversity responses to external disturbances, suggesting that a multi-decadal view needs to be taken when designing effective conservation management of freshwater ecosystems under current global warming.

Purpose: Living alone is increasing and associated with health and social risks. Aphasia compounds these risks but there is little research on how living alone interacts with aphasia. This study is a preliminary exploration of this issue. Method: Five people with aphasia who lived alone participated in two supported semi-structured interviews, with the second interview including sharing an artefact that held significance for living alone with aphasia. Interviews were recorded, transcribed verbatim, and analysed through reflexive thematic analysis. Result: Four themes encompassed meaning-making about living alone with aphasia: relationships and reliance on others; risk, vulnerability, and uncertainty; loneliness and time alone; self-reliance and the need to keep busy. Participants had to continuously manage and renegotiate daily challenges around living alone with aphasia. Conclusion: Living alone increases the risk of loneliness. For people with aphasia, the buffer against loneliness provided by social connection and meaningful activity may be more difficult to achieve because of communication challenges. While experiences vary, reliance on others, managing practical and administrative tasks, and negotiating risks are all important issues when alone. The intersection of living alone, loneliness, and living with aphasia needs more research, and more explicit clinical focus when discussing and planning intervention and support.

Purpose: To investigate the use of two versions of a simulation-based learning experience (SBLE) to decrease speech-language pathology (SLP) students’ anxiety and increase their confidence and sense of preparedness for clinical placements. Method: Two cohorts of third-year SLP students (n = 33) participated in a mixed-methods study with each cohort completing one version of the SBLE. Participants completed pre- and post-program quantitative ratings of anxiety, confidence, and preparedness for clinical placements and participated in focus groups. Three clinical educators also provided qualitative data in debriefs and interviews. Result: Significant decreases in student ratings of anxiety, and increases in confidence and sense of preparedness, were found for participants from both versions of the SBLE. No significant differences were found between changes in each measure between the two groups. Qualitative data from the student focus groups and clinical educator interviews described affective changes in the students, which concurred with the quantitative results. Conclusion: Results suggest this SBLE can be used to improve SLP students’ self-perceptions of readiness for clinical placements. Comparable outcomes can be achieved for students using the shorter, less resource intensive version of the SBLE program, with reduced costs, to overcome barriers to its implementation.

Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next-generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Ae. aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to effectively control wild populations of disease vectors.

We use both chirped-pulse Fourier transform and frequency modulated absorption spectroscopy to study the rotational spectrum of 2-methoxyethanol in several frequency regions ranging from 8.7-500 GHz. The resulting rotational parameters permitted a search for this molecule in Atacama Large Millimeter/submillimeter Array (ALMA) observations toward the massive protocluster NGC 6334I as well as source B of the low-mass protostellar system IRAS 16293-2422. 25 rotational transitions are observed in the ALMA Band 4 data toward NGC 6334I, resulting in the first interstellar detection of 2-methoxyethanol. A column density of $1.3_{-0.9}^{+1.4} \times 10^{17}$ cm$^{-2}$ is derived at an excitation temperature of $143_{-39}^{+31}$ K. However, molecular signal is not observed in the Band 7 data toward IRAS 16293-2422B and an upper limit column density of $2.5 \times 10^{15}$ cm$^{-2}$ is determined. Various possible formation pathways--including radical recombination and insertion reactions--are discussed. We also investigate physical differences between the two interstellar sources that could result in the observed abundance variations., Comment: Accepted for publication in The Astrophysical Journal Letters

Much of the information gleaned from observations of star-forming regions comes from the analysis of their molecular emission spectra, particularly in the radio regime. The time-consuming nature of fitting synthetic spectra to observations interactively for such line-rich sources, however, often results in such analysis being limited to data extracted from a single-dish observation or a handful of pixels from an interferometric observation. Yet, star-forming regions display a wide variety of physical conditions that are difficult, if not impossible, to accurately characterize with such a limited number of spectra. We have developed an automated fitting routine that visits every pixel in the field of view of an ALMA data cube and determines the best-fit physical parameters, including excitation temperature and column densities, for a given list of molecules. In this proof-of-concept work, we provide an overview of the fitting routine and apply it to 0".26, 1.1 km s$^{-1}$ resolution ALMA observations of two sites of massive star-formation in NGC 6334I. Parameters were found for 21 distinct molecules by generating synthetic spectra across 7.48 GHz of spectral bandwidth between 280 and 351 GHz. Spatial images of the derived parameters for each of the > 8000 pixels are presented with special attention paid to the C$_2$H$_4$O$_2$ isomers and their relative variations. We highlight the greater scientific utility of the column density and velocity images of individual molecules compared to traditional moment maps of single transitions., Comment: 40 pages, 71 figures, accepted for publication in The Astrophysical Journal

INTRODUCTION: People with aphasia following stroke experience disproportionally poor outcomes, yet there is no comprehensive approach to measuring the quality of aphasia services. The Meaningful Evaluation of Aphasia SeRvicES (MEASuRES) minimum dataset was developed in partnership with people with lived experience of aphasia, clinicians and researchers to address this gap. It comprises sociodemographic characteristics, quality indicators, treatment descriptors and outcome measurement instruments. We present a protocol to pilot the MEASuRES minimum dataset in clinical practice, describe the factors that hinder or support implementation and determine meaningful thresholds of clinical change for core outcome measurement instruments. METHODS AND ANALYSIS: This research aims to deliver a comprehensive quality assessment toolkit for poststroke aphasia services in four studies. A multicentre pilot study (study 1) will test the administration of the MEASuRES minimum dataset within five Australian health services. An embedded mixed-methods process evaluation (study 2) will evaluate the performance of the minimum dataset and explore its clinical applicability. A consensus study (study 3) will establish consumer-informed thresholds of meaningful change on core aphasia outcome constructs, which will then be used to establish minimal important change values for corresponding core outcome measurement instruments (study 4). ETHICS AND DISSEMINATION: Studies 1 and 2 have been registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623001313628). Ethics approval has been obtained from the Royal Brisbane and Women's Hospital (HREC/2023/MNHB/95293) and The University of Queensland (2022/HE001946 and 2023/HE001175). Study findings will be disseminated through peer-reviewed publications, conference presentations and engagement with relevant stakeholders including healthcare providers, policy-makers, stroke and rehabilitation audit and clinical quality registry cus

Recent years have seen broad observational support for the presence of a clumpy component within the circumnuclear gas around SMBHs. In the X-ray band, individual clouds can manifest themselves when they transit the line of sight to the X-ray corona, temporarily obscuring the X-ray continuum and thereby indicating the characteristics and location of these clouds. X-ray flux monitoring with SRG/eROSITA has revealed that in the Seyfert 1 AGN EC 04570-5206, the soft X-ray flux dipped abruptly for about 10-18 months over 2020-2021, only to recover and then drop a second time by early 2022. Here, we investigate whether these flux dips and recoveries could be associated with cloud occultation events. We complemented the eROSITA scans with multiwavelength follow-up observations, including X-ray/UV observations with Swift, XMM-Newton, and NICER, along with ground-based optical photometric and spectroscopic observations to investigate the spectral and flux variability. XMM-Newton spectra confirm that the soft X-ray flux dips were caused by partial-covering obscuration by two separate clouds. The 2020-2021 event was caused by a cloud with column density near 1e22 /cm2 and a covering fraction near 0.6. The cloud in the 2022 event had a column density near 3e23 /cm2 and a covering fraction near 0.8. The optical/UV continuum flux varied minimally and the optical emission line spectra showed no variability in Balmer profiles or intensity. The transiting gas clouds are neutral or lowly-ionized, while the lower limits on their radial distances are commensurate with the dust sublimation zone (cloud 1) or the optical broad line region (cloud 2). One possible explanation is a dust-free, outflowing wind with embedded X-ray clumps. These events are the first cloud obscuration events detected in a Seyfert galaxy using eROSITA's X-ray monitoring capabilities., Comment: Accepted for publication in Astronomy and Astrophysics

Agriculture is expanding rapidly across the tropics. While cultivation can boost socioeconomic conditions and food security, it also threatens native ecosystems. Oil palm (Elaeis guineensis), which is grown pantropically, is the most productive vegetable oil crop worldwide. The impacts of oil palm cultivation have been studied extensively in Southeast Asia and – to a lesser extent – in Latin America but, in comparison, very little is known about its impacts in Africa: oil palm's native range, and where cultivation is expanding rapidly. In this paper, we introduce a large-scale research programme – the Sustainable Oil Palm in West Africa (SOPWA) Project – that is evaluating the relative ecological impacts of oil palm cultivation under traditional (i.e., by local people) and industrial (i.e., by a large-scale corporation) management in Liberia. Our paper is twofold in focus. First, we use systematic mapping to appraise the literature on oil palm research in an African context, assessing the geographic and disciplinary focus of existing research. We found 757 publications occurring in 36 African countries. Studies tended to focus on the impacts of palm oil consumption on human health and wellbeing. We found no research that has evaluated the whole-ecosystem (i.e., multiple taxa and ecosystem functions) impacts of oil palm cultivation in Africa, a knowledge gap which the SOPWA Project directly addresses. Second, we describe the SOPWA Project's study design and—using canopy cover, ground vegetation cover, and soil temperature data as a case study—demonstrate its utility for assessing differences between areas of rainforest and oil palm agriculture. We outline the socioecological data collected by the SOPWA Project to date and describe the potential for future research, to encourage new collaborations and additional similar projects of its kind in West Africa. Increased research in Africa is needed urgently to understand the combined ecological and sociocultural impacts o

Through an investigation of the ceramics from the site of Mochlos, East Crete, Greece, this dissertation seeks to understand how Early Bronze Age Eurasian communities constructed and maintained socioeconomic institutions. Based on this research, I propose that the Early Bronze Age Mochlos community utilized social memory as a tool to generate cooperative institutions and maintain group cohesion. These institutions are reflected in the household assemblages through conformity to Western Anatolian and Cycladic pottery, textile, and metallurgical traditions and the adoption of Early and Middle Prepalatial wares from the Mirabello and the South Coast near Ierapetra. This balance created a uniquely Mochlosian culture that reinforced cooperative institutions by simultaneously connecting the community to its past and its present, both in their daily lives and through ceremonial activities in the cemetery. In the Late Prepalatial Period, however, Mochlos intensified their consumption of imported Mirabello wares and decreased their reliance on locally produced traditional pottery. This change in preference indicates a shift from the cooperative institutions of the Early and Middle Prepalatial period toward more individualistic, competitive institutions at Mochlos. This transition eroded group cohesion at Mochlos and may explain the decline in population that is evident at the beginning of the Protopalatial period.

Introduction: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m2 in the avacopan group and 4.1 ml/min per 1.73 m2 in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR ≤20 ml/min per 1.73 m2. Methods: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. Results: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR ≤20 ml/min per 1.73 m2. At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m2 in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was ≥2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m2, respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. Conclusion: Among patients with baseline eGFR ≤20 ml/min per 1.73 m2 in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

In 1901, while vacationing in New York's Adirondack Mountains, Vice President Theodore Roosevelt received news that President McKinley had been shot and was not expected to live. By the time Roosevelt arrived at the home of his friend Ansley Wilcox in Buffalo (New York), the President was dead. Roosevelt was inaugurated in the library of his friend's stately Greek Revival home. This lesson plan is based on the National Register of Historic Places registration file for the Theodore Roosevelt Inaugural National Historic Site (Ansley Wilcox House) and other source material. The lesson can be used in U.S. history, social studies, and geography courses in units on Theodore Roosevelt's presidency, the Progressive Era, or government and politics. The teacher materials section provides general information, gives educational objectives for students, discusses visiting the site, lists supplementary resources, and describes how to use the lesson plans. The student materials section includes: "Getting Started"; "Photograph Analysis Worksheet"; "Setting the Stage"; "Locating the Site" (Map: New York State); "Determining the Facts" (Reading: It is a dreadful thing to come to the Presidency this way; Document: Illustrated Buffalo Express, Sept. 15, 1901; Readings: Roosevelt's First Presidential Proclamation; The Bully Pulpit); "Visual Evidence" (Drawings: Delaware Avenue, Buffalo, NY, 1873; Sketch of the Inauguration; Photos: Wilcox Library today; Wilcox House, 1901; Wilcox House, 1971); and "Putting It All Together" (Activities: Where Were You on the Day, Snapshot of History, Buildings That Have Witnessed History). (BT)

CRISPR diagnostics have recently emerged as powerful diagnostic tools for the rapid detection of infections. The ultimate goal is to develop these diagnostics for the point of care, where patients quickly receive and easily interpret results. Although they are in their infancy, the COVID-19 pandemic has accelerated innovation of CRISPR diagnostics and led to an explosion of improvements to these systems. Challenges that have impeded the implementation at the point of care have been addressed, and CRISPR diagnostics have been dramatically simplified. Here we outline recent developments and advancements in CRISPR diagnostics that have pushed these technologies to the point of care.

Escalating vector disease burdens pose significant global health risks, as such innovative tools for targeting mosquitoes are critical. CRISPR-Cas technologies have played a crucial role in developing powerful tools for genome manipulation in various eukaryotic organisms. Although considerable efforts have focused on utilizing class II type II CRISPR-Cas9 systems for DNA targeting, these modalities are unable to target RNA molecules, limiting their utility against RNA viruses. Recently, the Cas13 family has emerged as an efficient tool for RNA targeting; however, the application of this technique in mosquitoes, particularly Aedes aegypti, has yet to be fully realized. In this study, we engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR-Cas13 and its potent collateral activity. REAPER remains concealed within the mosquito until an infectious blood meal is uptaken. Upon target viral RNA infection, REAPER activates, triggering programmed destruction of its target arbovirus such as chikungunya. Consequently, Cas13-mediated RNA targeting significantly reduces viral replication and viral prevalence of infection, and its promiscuous collateral activity can even kill infected mosquitoes within a few days. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission.

Escalating vector disease burdens pose significant global health risks, so innovative tools for targeting mosquitoes are critical. We engineered an antiviral strategy termed REAPER (vRNA Expression Activates Poisonous Effector Ribonuclease) that leverages the programmable RNA-targeting capabilities of CRISPR Cas13 and its potent collateral activity. Akin to a stealthy Trojan Horse hiding in stealth awaiting the presence of its enemy, REAPER remains concealed within the mosquito until an infectious blood meal is up taken. Upon target viral RNA infection, REAPER activates, triggering programmed destruction of its target arbovirus such as chikungunya. Consequently, Cas13 mediated RNA targeting significantly reduces viral replication and its promiscuous collateral activity can even kill infected mosquitoes. This innovative REAPER technology adds to an arsenal of effective molecular genetic tools to combat mosquito virus transmission.

The effect of treatment dose on recovery of post-stroke aphasia is not well understood. Inconsistent conceptualization, measurement, and reporting of the multiple dimensions of dose hinders efforts to evaluate dose-response relations in aphasia rehabilitation research. We review the state of dose conceptualization in aphasia rehabilitation and compare the applicability of 3 existing dose frameworks to aphasia rehabilitation research-the Frequency, Intensity, Time, and Type (FITT) principle, the Cumulative Intervention Intensity (CII) framework, and the Multidimensional Dose Articulation Framework (MDAF). The MDAF specifies dose in greater detail than the CII framework and the FITT principle. On this basis, we selected the MDAF to be applied to 3 diverse examples of aphasia rehabilitation research. We next critically examined applicability of the MDAF to aphasia rehabilitation research and identified the next steps needed to systematically conceptualize, measure, and report the multiple dimensions of dose, which together can progress understanding of the effect of treatment dose on outcomes for people with aphasia after stroke. Further consideration is required to enable application of this framework to aphasia interventions that focus on participation, personal, and environmental interventions and to understand how the construct of episode difficulty applies across therapeutic activities used in aphasia interventions.

OBJECTIVE: To describe the costs of hospital care for acute stroke for patients with aphasia or dysarthria. DESIGN: Observational study from the Stroke123 project. SETTING: Data from patients admitted with stroke (2009-2013) from 22 hospitals in Queensland participating in the Australian Stroke Clinical Registry (AuSCR) were linked to administrative datasets. PARTICIPANTS: Communication impairments were identified using International Classification of Diseases, 10th Revision, Australian Modification codes. Overall, 1043 of 4195 (25%) patients were identified with aphasia (49% were women; median age 78 years; 83% with ischemic stroke), and 1005 (24%) with dysarthria (42% were women; median age 76 years; 85% with ischemic stroke). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Linked patient-level, hospital clinical costing related to the stroke, were adjusted to 2013/2014 Australian dollars (AU$, US$ conversion x 0.691) using recommended national price indices and multivariable regression analysis with clustering by hospital performed. RESULTS: Compared with patients without aphasia, the median hospital costs/patient were greater for those with aphasia for medical (aphasia AU$2273 vs AU$1727, P<.001), nursing (aphasia AU$3829 vs AU$2748, P<.001) and allied health services (aphasia AU$1138 vs AU$720, P<.001). Similarly, costs were greater for patients with dysarthria compared with those without dysarthria. Adjusted median total costs were AU$2882 greater for patients with aphasia compared with patients without aphasia (95% confidence interval, AU$1880-3884), and AU$843 greater for patients with dysarthria compared with those without dysarthria (95% confidence interval, AU$-301 to 1987). CONCLUSIONS: People with communication impairment after stroke incur greater hospital costs, in particular for medical, allied health, and nursing resources.

Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to control wild populations, safely curtailing disease transmission.

Item does not contain fulltext, INTRODUCTION: Accurate and standardized phenotypic descriptions are essential in diagnosing rare diseases and discovering new diseases, and the Human Phenotype Ontology (HPO) system was developed to provide a rich collection of hierarchical phenotypic descriptions. However, although the HPO terms for inborn errors of immunity have been improved and curated, it has not been investigated whether this curation improves the diagnosis of systemic autoinflammatory disease (SAID) patients. Here, we aimed to study if improved HPO annotation for SAIDs enhanced SAID identification and to demonstrate the potential of phenotype-driven genome diagnostics using curated HPO terms for SAIDs. METHODS: We collected HPO terms from 98 genetically confirmed SAID patients across eight different European SAID expertise centers and used the LIRICAL (Likelihood Ratio Interpretation of Clinical Abnormalities) computational algorithm to estimate the effect of HPO curation on the prioritization of the correct SAID for each patient. RESULTS: Our results show that the percentage of correct diagnoses increased from 66% to 86% and that the number of diagnoses with the highest ranking increased from 38 to 45. In a further pilot study, curation also improved HPO-based whole-exome sequencing (WES) analysis, diagnosing 10/12 patients before and 12/12 after curation. In addition, the average number of candidate diseases that needed to be interpreted decreased from 35 to 2. DISCUSSION: This study demonstrates that curation of HPO terms can increase identification of the correct diagnosis, emphasizing the high potential of HPO-based genome diagnostics for SAIDs.

BACKGROUND: Aphasia is a common consequence of stroke, and people who live with this condition experience poor outcomes. Adherence to clinical practice guidelines can promote high-quality service delivery and optimize patient outcomes. However, there are currently no high-quality guidelines specific to post-stroke aphasia management. AIMS: To identify and evaluate recommendations from high-quality stroke guidelines that can inform aphasia management. SUMMARY OF REVIEW: We conducted an updated systematic review in accordance with PRISMA guidelines to identify high-quality clinical guidelines published between January 2015 and October 2022. Primary searches were performed using electronic databases: PubMed, EMBASE, CINAHL, and Web of Science. Gray literature searches were conducted using Google Scholar, guideline databases, and stroke websites. Clinical practice guidelines were evaluated using the Appraisal of Guidelines and Research and Evaluation (AGREE II) tool. Recommendations were extracted from high-quality guidelines (scored > 66.7% on Domain 3: "Rigor of Development"), classified as aphasia-specific or aphasia-related, and categorized into clinical practice areas. Evidence ratings and source citations were assessed, and similar recommendations were grouped. Twenty-three stroke clinical practice guidelines were identified and 9 (39%) met our criteria for rigor of development. From these guidelines, 82 recommendations for aphasia management were extracted: 31 were aphasia-specific, 51 aphasia-related, 67 evidence-based, and 15 consensus-based. CONCLUSION: More than half of stroke clinical practice guidelines identified did not meet our criteria for rigorous development. We identified 9 high-quality guidelines and 82 recommendations to inform aphasia management. Most recommendations were aphasia-related; aphasia-specific recommendation gaps were identified in three clinical practice areas: "accessing community supports," "return to work, leisure, driving," and "i

The effect of treatment dose on recovery of post-stroke aphasia is not well understood. Inconsistent conceptualization, measurement, and reporting of the multiple dimensions of dose hinders efforts to evaluate dose-response relations in aphasia rehabilitation research. We review the state of dose conceptualization in aphasia rehabilitation and compare the applicability of 3 existing dose frameworks to aphasia rehabilitation research—the Frequency, Intensity, Time, and Type (FITT) principle, the Cumulative Intervention Intensity (CII) framework, and the Multidimensional Dose Articulation Framework (MDAF). The MDAF specifies dose in greater detail than the CII framework and the FITT principle. On this basis, we selected the MDAF to be applied to 3 diverse examples of aphasia rehabilitation research. We next critically examined applicability of the MDAF to aphasia rehabilitation research and identified the next steps needed to systematically conceptualize, measure, and report the multiple dimensions of dose, which together can progress understanding of the effect of treatment dose on outcomes for people with aphasia after stroke. Further consideration is required to enable application of this framework to aphasia interventions that focus on participation, personal, and environmental interventions and to understand how the construct of episode difficulty applies across therapeutic activities used in aphasia interventions.

We present a study of the physical and chemical properties of the Extended Green Object (EGO) G19.01$-$0.03 using sub-arcsecond angular resolution Atacama Large Millimeter/submillimeter Array (ALMA) 1.05mm and Karl G. Jansky Very Large Array (VLA) 1.21cm data. G19.01$-$0.03 MM1, the millimetre source associated with the central massive young stellar object (MYSO), appeared isolated and potentially chemically young in previous Submillimeter Array observations. In our $\sim0.4''$-resolution ALMA data, MM1 has four low-mass millimetre companions within 0.12pc, all lacking maser or outflow emission, indicating they may be prestellar cores. With a rich ALMA spectrum full of complex organic molecules, MM1 does not appear chemically young, but has molecular abundances typical of high-mass hot cores in the literature. At the 1.05mm continuum peak of MM1, $\mathrm{N}(\mathrm{CH}_{3}\mathrm{OH})=(2.22\pm0.01)\times10^{18}$cm$^{-2}$ and $T_{\mathrm{ex}} = 162.7\substack{+0.3 \\ -0.5}$K based on pixel-by-pixel Bayesian analysis of LTE synthetic methanol spectra across MM1. Intriguingly, the peak CH$_{3}$OH $T_{\mathrm{ex}}=165.5\pm0.6$ K is offset from MM1's millimetre continuum peak by $0.22''\sim880$au, and a region of elevated CH$_{3}$OH $T_{\mathrm{ex}}$ coincides with free-free VLA 5.01cm continuum, adding to the tentative evidence for a possible unresolved high-mass binary in MM1. In our VLA 1.21cm data, we report the first NH$_{3}$(3,3) maser detections towards G19.01$-$0.03, along with candidate 25GHz CH$_{3}$OH $5(2,3)-5(1,4)$ maser emission; both are spatially and kinematically coincident with 44GHz Class I CH$_{3}$OH masers in the MM1 outflow. We also report the ALMA detection of candidate 278.3GHz Class I CH$_{3}$OH maser emission towards this outflow, strengthening the connection of these three maser types to MYSO outflows., Comment: 24 pages, 15 figures, 7 tables, Accepted for publication in MNRAS

Complex organic molecules (COMs) have been observed to be abundant in the gas phase toward protostars. Deep line surveys have been carried out only for a limited number of well-known high-mass star forming regions using the Atacama Large Millimeter/submillimeter Array (ALMA), which has unprecedented resolution and sensitivity. Statistical studies on oxygen-bearing COMs (O-COMs) in high-mass protostars using ALMA are still lacking. With the recent CoCCoA survey, we are able to determine the column density ratios of six O-COMs with respect to methanol (CH$_3$OH) in a sample of 14 high-mass protostellar sources to investigate their origin through ice and/or gas-phase chemistry. The selected species are: acetaldehyde (CH$_3$CHO), ethanol (C$_2$H$_5$OH), dimethyl ether (DME, CH$_3$OCH$_3$), methyl formate (MF, CH$_3$OCHO), glycolaldehyde (GA, CH$_2$OHCHO), and ethylene glycol (EG, (CH$_2$OH)$_2$). DME and MF have the highest and most constant ratios within one order of magnitude, while the other four species have lower ratios and exhibit larger scatter by 1-2 orders of magnitude. We compare the O-COM ratios of high-mass CoCCoA sources with those of 5 low-mass protostars available from the literature, along with the results from experiments and simulations. We find that the O-COM ratios with respect to methanol are on the same level in both the high- and low-mass samples, which suggests that these species are mainly formed in similar environments during star formation, probably in ice mantles on dust grains during early pre-stellar stages. Current simulations and experiments can reproduce most observational trends with a few exceptions, and hypotheses exist to explain the differences between observations and simulations/experiments, such as the involvement of gas-phase chemistry and different emitting areas of molecules., Comment: Accepted for publication in Astronomy & Astrophysics. 17 pages and 7 figures in the main body, 15 pages and 8 figures in the appendix

Changing-look active galactic nuclei (CL-AGN) have been observed to change optical spectral type. Mrk 1018 is unique: first classified as a type 1.9 Seyfert galaxy, it transitioned to a type 1 before returning to its initial classification after approximately 30 years. We present a high-cadence monitoring programme that caught a major outburst in 2020. Due to sunblock, only the decline could be observed. We studied X-ray, UV, optical, and IR before and after the outburst to investigate the responses of the AGN structures. We derived a u'-band light curve of the AGN contribution alone. The flux increased by a factor of the order of 13. We confirmed this in other optical bands and determined the shape and speed of the decline in each waveband. The shapes of H beta and H alpha were analysed before and after the event. Two XMM-Newton observations from before and after the outburst were also exploited. The outburst is asymmetric, with a swifter rise than decline. The decline is best fit by a linear function, ruling out a tidal disruption event. The optical spectrum shows no change approximately 8 months before and 17 months after. The UV flux increased slightly after the outburst but the X-ray primary flux is unchanged. However, the 6.4 keV Iron line has doubled in strength. IR data taken 13 days after the observed optical peak show an increased emission level. Calculating the distance of the broad-line region and inner edge of the torus from the supermassive black hole can explain the multi-wavelength response to the outburst, in particular: i) the unchanged H beta and H alpha lines, ii) the unchanged primary X-ray spectral components, iii) the rapid and extended infrared response, as well as iv) the enhanced emission of the reflected 6.4 keV line. The outburst was due to a dramatic and short-lasting change in the intrinsic accretion rate. We discuss different models as potential causes., Comment: Accepted for publication in A&A

We describe the calibration and imaging heuristics developed and deployed in the ALMA interferometric data processing pipeline, as of ALMA Cycle 9. The pipeline software framework is written in Python, with each data reduction stage layered on top of tasks and toolkit functions provided by the Common Astronomy Software Applications package. This framework supports a variety of tasks for observatory operations, including science data quality assurance, observing mode commissioning, and user reprocessing. It supports ALMA and VLA interferometric data along with ALMA and NRO45m single dish data, via different stages and heuristics. In addition to producing calibration tables, calibrated measurement sets, and cleaned images, the pipeline creates a WebLog which serves as the primary interface for verifying the data quality assurance by the observatory and for examining the contents of the data by the user. Following the adoption of the pipeline by ALMA Operations in 2014, the heuristics have been refined through annual development cycles, culminating in a new pipeline release aligned with the start of each ALMA Cycle of observations. Initial development focused on basic calibration and flagging heuristics (Cycles 2-3), followed by imaging heuristics (Cycles 4-5), refinement of the flagging and imaging heuristics with parallel processing (Cycles 6-7), addition of the moment difference analysis to improve continuum channel identification (2020 release), addition of a spectral renormalization stage (Cycle 8), and improvement in low SNR calibration heuristics (Cycle 9). In the two most recent Cycles, 97% of ALMA datasets were calibrated and imaged with the pipeline, ensuring long-term automated reproducibility. We conclude with a brief description of plans for future additions, including self-calibration, multi-configuration imaging, and calibration and imaging of full polarization data., Comment: Accepted for publication by Publications of the Astronomical Society of the Pacific, 65 pages, 20 figures, 10 tables, 2 appendices. Small corrections and additions from the proof stage have been applied

High-mass protostars (M$_{\star} >$ 8 M$_{\odot}$) are thought to gain the majority of their mass via short, intense bursts of growth. This episodic accretion is thought to be facilitated by gravitationally unstable and subsequently inhomogeneous accretion disks. Limitations of observational capabilities, paired with a lack of observed accretion burst events has withheld affirmative confirmation of the association between disk accretion, instability and the accretion burst phenomenon in high-mass protostars. Following its 2019 accretion burst, a heat-wave driven by a burst of radiation propagated outward from the high-mass protostar G358.93-0.03-MM1. Six VLBI (very long baseline interferometry) observations of the raditively pumped 6.7 GHz methanol maser were conducted during this period, tracing ever increasing disk radii as the heat-wave propagated outward. Concatenating the VLBI maps provided a sparsely sampled, milliarcsecond view of the spatio-kinematics of the accretion disk covering a physical range of $\sim$ 50 - 900 AU. We term this observational approach `heat-wave mapping'. We report the discovery of a Keplerian accretion disk with a spatially resolved four-arm spiral pattern around G358.93-0.03-MM1. This result positively implicates disk accretion and spiral arm instabilities into the episodic accretion high-mass star formation paradigm., Comment: Published in Nature Astronomy in 2023

High-mass stars are thought to accumulate much of their mass via short, infrequent bursts of disk-aided accretion. Such accretion events are rare and difficult to observe directly but are known to drive enhanced maser emission. In this Letter we report high-resolution, multi-epoch methanol maser observations toward G358.93-0.03 which reveal an interesting phenomenon; the sub-luminal propagation of a thermal radiation "heat-wave" emanating from an accreting high-mass proto-star. The extreme transformation of the maser emission implies a sudden intensification of thermal infrared radiation from within the inner (40 mas, 270 au) region. Subsequently, methanol masers trace the radial passage of thermal radiation through the environment at $\geq$ 4-8\% the speed of light. Such a high translocation rate contrasts with the $\leq$ 10 km s$^{-1}$ physical gas motions of methanol masers typically observed using very long baseline interferometry (VLBI). The observed scenario can readily be attributed to an accretion event in the high-mass proto-star G358.93-0.03-MM1. While being the third case in its class, G358.93-0.03-MM1 exhibits unique attributes hinting at a possible `zoo' of accretion burst types. These results promote the advantages of maser observations in understanding high-mass star formation, both through single-dish maser monitoring campaigns and via their international cooperation as VLBI arrays., Comment: Published in Nature Astronomy in 2020

We report the discovery and spectroscopic identification of the bright doubly lensed quasar eRASS1 J050129.5-073309 at redshift $z=2.47$, selected from the first all-sky survey of the ${\it Spectrum\; Roentgen\; Gamma\; (SRG)}$ eROSITA telescope and the ${\it Gaia}$ EDR3 catalog. We systematically search for extragalactic sources with eROSITA X-ray positions having multiple ${\it Gaia}$ counterparts and have started spectroscopic follow-up of the most promising candidates using long-slit spectroscopy with NTT/EFOSC2 to confirm the lens nature. The two images are separated by $2.7''$ and their average ${\it Gaia}$ ${\it g}$-band magnitudes are 16.95 and 17.33. Legacy Survey DR10 imaging and image modeling reveal both the lensing galaxy and tentatively the lensed image of the quasar host galaxy. Archival optical light curves show evidence of a variability time delay with the fainter component lagging the brighter by about 100 days. The fainter image has also decreased its brightness by about 1 magnitude since 2019. This dimming was still obvious at the time of the spectroscopic observations and is probably caused by microlensing. The optical spectroscopic follow-up obtained from NTT/EFOSC2 and the evidence provided by the imaging and timing analysis allow us to confirm the lensed nature of eRASS1 J050129.5-073309., Comment: Accepted for publication in A&A

Introduction: Accurate and standardized phenotypic descriptions are essential in diagnosing rare diseases and discovering new diseases, and the Human Phenotype Ontology (HPO) system was developed to provide a rich collection of hierarchical phenotypic descriptions. However, although the HPO terms for inborn errors of immunity have been improved and curated, it has not been investigated whether this curation improves the diagnosis of systemic autoinflammatory disease (SAID) patients. Here, we aimed to study if improved HPO annotation for SAIDs enhanced SAID identification and to demonstrate the potential of phenotype-driven genome diagnostics using curated HPO terms for SAIDs. Methods: We collected HPO terms from 98 genetically confirmed SAID patients across eight different European SAID expertise centers and used the LIRICAL (Likelihood Ratio Interpretation of Clinical Abnormalities) computational algorithm to estimate the effect of HPO curation on the prioritization of the correct SAID for each patient. Results: Our results show that the percentage of correct diagnoses increased from 66% to 86% and that the number of diagnoses with the highest ranking increased from 38 to 45. In a further pilot study, curation also improved HPO-based whole-exome sequencing (WES) analysis, diagnosing 10/12 patients before and 12/12 after curation. In addition, the average number of candidate diseases that needed to be interpreted decreased from 35 to 2. Discussion: This study demonstrates that curation of HPO terms can increase identification of the correct diagnosis, emphasizing the high potential of HPO-based genome diagnostics for SAIDs.

Introduction: There is limited evidence on the costs and outcomes of patients with aphasia after stroke. The aim of this study was to estimate costs in patients with aphasia after stroke according to the aphasia therapies provided. Methods: A three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment trial conducted in Australia and New Zealand. Usual ward-based care (Usual Care) was compared to additional usual ward-based therapy (Usual Care Plus) and a prescribed and structured aphasia therapy program in addition to Usual Care (the VERSE intervention). Information about healthcare utilization and productivity were collected to estimate costs in Australian dollars for 2017–18. Multivariable regression models with bootstrapping were used to estimate differences in costs and outcomes (clinically meaningful change in aphasia severity measured by the WAB-R-AQ). Results: Overall, 202/246 (82%) participants completed follow-up at 26 weeks. Median costs per person were $23,322 (Q1 5,367, Q3 52,669, n = 63) for Usual Care, $26,923 (Q1 7,303, Q3 76,174, n = 70) for Usual Care Plus and $31,143 (Q1 7,001. Q3 62,390, n = 69) for VERSE. No differences in costs and outcomes were detected between groups. Usual Care Plus was inferior (i.e. more costly and less effective) in 64% of iterations, and in 18% was less costly and less effective compared to Usual Care. VERSE was inferior in 65% of samples and less costly and less effective in 12% compared to Usual Care. Conclusion: There was limited evidence that additional intensively delivered aphasia therapy within the context of usual acute care provided was worthwhile in terms of costs for the outcomes gained.

Chronic low back pain (CLBP) is a worldwide epidemic, with a prevalence rate of 75–84% in developed countries. With the prevalence increasing, health-care professionals must question current best practice guidelines. In 2014, spinal neurosurgeon and back pain rehabilitation specialist Dr. David Johnson developed a unique back pain rehabilitation program referred to as NearoHAB®. The program’s uniqueness is founded on the principle that effective rehabilitation must eliminate the root cause of pain symptoms. The NeuroHAB® 8-week Movement therapy program aims to reverse movement dysfunction by restoring central nervous system-derived motor patterns based on proficient spinopelvic biomechanics for bending activities of daily living. To date, no other rehabilitation methodology adopts a movement dysfunction cause-based clinical model for back pain symptoms or includes a framework for what healthy lumbar pelvic movement should resemble. Over the course of the 8-week program, each participant is gradually upskilled, developing new default movement proficiency and improved biomechanics, in efforts to downregulate pain, improve disability, and increase functional movement capacity, creating a positive feedback loop for further progress. The leading question of this study is “How does functional movement-based therapy impact chronic low back pain?” Ten sets of participant details were selected at random and retrieved from the NeuroHAB® 8-week program database of 2020. All participants presented with CLBP, and two oswestry disability index (ODI) scores were documented – the first at the beginning of the 8-week program, and the second after the NeuroHAB® intervention. ODI scores were collated and the pre- and post-program results were measured and compared quantitatively through a paired t-test to determine the statistical significance of improvement. Results showed a two-tailed P=0.05 indicating that there was a significant difference between the pre- and post-data (0.0024).

The authors regret < for the oversight to mention that this work has been done on behalf of the Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO) >. The authors would like to apologise for any inconvenience caused. ____________________________ DOI of original article: < 10.1016/j.semarthrit.2022.151957>